Wednesday, January 13, 1999 Published at 17:00 GMTHealthFat hope for an obesity cureObesity is a common problem in the western worldScientists across the world are searching for a cure for obesity - but a miracle cure free of side-effects could be a long way off.

The number of people who are obese is soaring. Half the British population is overweight.

Scientists have only recently begun to understand the body's mechanisms for controlling its own weight.

Four years ago scientists working with mice discovered a hormone, leptin, which appears to control weight.

Leptin is produced by body fat, and travels up to the appetite control centre in the brain, the hypothalamus.

When the body loses fat the resulting lack of leptin stimulates appetite, and when fat accumulates the extra levels of leptin that are produced cause the hypothalamus to depress interest in food.

Therefore, body fat is maintained at a steady level, and makes dieting difficult. The mechanism can be altered, but it is easier to make the body gain weight, than to lose it.

Radical surgery

Shirley Rutherford underwent major surgery

When diets fail, some people opt for radical surgery. However, this can cause serious problems such as severe diarrhoea.

Shirley Rutherford underwent surgery to join her small intestine directly to her bowel, bypassing a six-metre section of her intestine, where food is absorbed.

She lost huge amounts of weight, but found that she also suffered from almost constant diarrhoea.

"I lost lots of weight. It just fell off me by the week," she said. "You did not have to diet at all, you could eat absolutely everything.

"My hunger was insatiable, but I was in the toilet 70% of the day."

It took 15 years for Shirley to develop serious physical problems associated with malnutrition. She developed problems with her joints, haemorrhaging and scurvy.

Eventually, she had to undergo emergency surgery to reconnect her intestines. Her weight went back up, but the operation saved her life.

Drug alternatives

Other people desperate to lose weight have tried other options, such as the dangerous addictive drug amphetamine.

Other diet drugs act on the hypothalamus to suppress appetite. In 1994 two drugs already on the market were combined.

Together Phentermine and Fenfluramine were potent and users lost as much as a fifth of their body weight.

The drugs took the US by storm, more than 6 million prescriptions were issued in 1996 alone.

However, the serious side effects of the drugs soon came to light. It causes a condition known as primary pulmonary hypertension, a constriction of the blood vessels which can cause widespread tissue damage leading to death.

The drug was shown to change the activity of nerve cells in many areas of the body. The combination was banned in 1997.

Fat people tried natural substitutes, such as herbs. A natural form of Phen-Fen was developed, but it did not depress the appetite sufficiently.

So instead, people have combined the main ingredient of the natural product, ephedrin, with two other drugs, caffeine and aspirin. The combination, known as The Stack, is widely available on the Internet. It works, but it is also dangerous.

There are no drugs on the market that target the appetite centres of the brain selectively.

Xenical, developed by the pharmaceutical firm Hoffman-La Roche, appeared to be the answer.

The drug changes the way that fatty food was digested, and stop fats being absorbed.

However, patients who tested it found they had to stick to a low fat diet for the compound to have any effect.

If they strayed from that diet, the resulting diarrhoea was extremely unpleasant. In addition Xenical only reduces body weight by 10% - clearly not enough for obese people.

The answer seems to lie in further research into leptin.

Fat mice released leptin

Experiments in mice have shown that as the animals gain weight, they release leptin. Normally this would lead to a suppression of the appetite, but in fat mice the brain's leptin receptors gradually become used to a higher level of leptin and fail to suppress appetite.

Dr Arthur Campfield, of Hoffman-La Roche, said: "We believe that there is some place in the leptin receptor that is broken so that obese people have almost no response when we give leptin into the brain."

Fat mice can only be made thin again by forcing them to stop eating. People need a more humane treeatment.

Scientists are now searching for a drug that will reverse the insensitivity of the leptin receptors in obese people and reduce the constant craving for food.

But this research could take ten years to come to fruition.

An alternative approach is to modify food to help people get slim.

Olestra was one of the first products to be included in food to make it "fat free".

Olestra is a fat that cannot be absorbed. However, it causes diarrhoea, and inhibits the absorption of nutrients.

Researchers are also developing food that naturally suppresses appetite by filling us up.

Carbohydrates are also natural appetite suppressors. They are bulky and cause the release hormones that make us feel full.

Meat protein contains amino acids that suppress appetite.

The next big step is to change what happens to food once it has been eaten.

Food supplements have been developed that reduce fat deposition and promote muscle growth.

Developments in food technology may work, but they are new and unproven. At present, the only solution guaranteed to produce fast results is radical surgery.

The real solution appears to be exercise. Not only does it burn up calories, it increases the potency of the nutrients that change body shape, and the effectiveness of the natural appetite suppressants in food.

The story of the search for a cure for obesity is told on the BBC Science programme Horizon "Fixing Fat" is broadcast on BBC Two at 2130 GMT on Thursday, 14 January, 1999.